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Acute Kidney Injury Sensitizes the Brain Vasculature to Ang II (Angiotensin II) Constriction via FGFBP1 (Fibroblast Growth Factor Binding Protein 1).
Zhao, Liang; Cao, Xiaoyun; Li, Lingli; Wang, Xiaohua; Wang, Qin; Jiang, Shan; Tang, Chun; Zhou, Suhan; Xu, Nan; Cui, Yu; Hu, Weipeng; Fei, Lingyan; Zheng, Zhihua; Chen, Limeng; Schmidt, Marcel O; Wei, Qichun; Zhao, Jingwei; Labes, Robert; Patzak, Andreas; Wilcox, Christopher S; Fu, Xiaodong; Wellstein, Anton; Lai, En Yin.
Affiliation
  • Zhao L; From the Department of Physiology, School of Basic Medical Sciences (L.Z., E.Y.L.), Guangzhou Medical University, China.
  • Cao X; Department of Physiology, School of Basic Medical Sciences (L.Z., XG., Q. Wang, S.J., S.Z., N.X., Y.C., W.H., E.Y.L.), Zhejiang University School of Medicine, Hangzhou, China.
  • Li L; Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany (L.Z., R.L., A.P., E.Y.L.).
  • Wang X; Department of Physiology, School of Basic Medical Sciences (L.Z., XG., Q. Wang, S.J., S.Z., N.X., Y.C., W.H., E.Y.L.), Zhejiang University School of Medicine, Hangzhou, China.
  • Wang Q; Division of Nephrology and Hypertension (L.L., C.S.W., E.Y.L.), Georgetown University, Washington, DC.
  • Jiang S; Department of Nephrology, Center of Nephrology and Urology. the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China (X.W., C.T., L.F., Z.Z.).
  • Tang C; Department of Physiology, School of Basic Medical Sciences (L.Z., XG., Q. Wang, S.J., S.Z., N.X., Y.C., W.H., E.Y.L.), Zhejiang University School of Medicine, Hangzhou, China.
  • Zhou S; Department of Physiology, School of Basic Medical Sciences (L.Z., XG., Q. Wang, S.J., S.Z., N.X., Y.C., W.H., E.Y.L.), Zhejiang University School of Medicine, Hangzhou, China.
  • Xu N; Department of Nephrology, Center of Nephrology and Urology. the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China (X.W., C.T., L.F., Z.Z.).
  • Cui Y; Department of Physiology, School of Basic Medical Sciences (L.Z., XG., Q. Wang, S.J., S.Z., N.X., Y.C., W.H., E.Y.L.), Zhejiang University School of Medicine, Hangzhou, China.
  • Hu W; Department of Physiology, School of Basic Medical Sciences (L.Z., XG., Q. Wang, S.J., S.Z., N.X., Y.C., W.H., E.Y.L.), Zhejiang University School of Medicine, Hangzhou, China.
  • Fei L; Department of Physiology, School of Basic Medical Sciences (L.Z., XG., Q. Wang, S.J., S.Z., N.X., Y.C., W.H., E.Y.L.), Zhejiang University School of Medicine, Hangzhou, China.
  • Zheng Z; Department of Physiology, School of Basic Medical Sciences (L.Z., XG., Q. Wang, S.J., S.Z., N.X., Y.C., W.H., E.Y.L.), Zhejiang University School of Medicine, Hangzhou, China.
  • Chen L; Department of Nephrology, Center of Nephrology and Urology. the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China (X.W., C.T., L.F., Z.Z.).
  • Schmidt MO; Department of Nephrology, Center of Nephrology and Urology. the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China (X.W., C.T., L.F., Z.Z.).
  • Wei Q; Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College (L.C.).
  • Zhao J; Lombardi Cancer Center (M.O.S., A.W.), Georgetown University, Washington, DC.
  • Labes R; Department of Radiation Oncology, Second Affiliated Hospital (Q. Wei), Zhejiang University School of Medicine, Hangzhou, China.
  • Patzak A; Department of Anatomy, Histology and Embryology, Institute of Neuroscience, School of Basic Medical Sciences (J.Z.), Zhejiang University School of Medicine, Hangzhou, China.
  • Wilcox CS; Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany (L.Z., R.L., A.P., E.Y.L.).
  • Fu X; Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany (L.Z., R.L., A.P., E.Y.L.).
  • Wellstein A; Division of Nephrology and Hypertension (L.L., C.S.W., E.Y.L.), Georgetown University, Washington, DC.
  • Lai EY; Department of Gynecology and Obstetrics, the Sixth Affiliated Hospital (X.F.), Guangzhou Medical University, China.
Hypertension ; 76(6): 1924-1934, 2020 12.
Article in En | MEDLINE | ID: mdl-33040621
Acute kidney injury (AKI) causes multiple organ dysfunction. Here, we identify a possible mechanism that can drive brain vessel injury after AKI. We induced 30-minute bilateral renal ischemia-reperfusion injury in C57Bl/6 mice and isolated brain microvessels and macrovessels 24 hours or 1 week later to test their responses to vasoconstrictors and found that after AKI brain vessels were sensitized to Ang II (angiotensin II). Upregulation of FGF2 (fibroblast growth factor 2) and FGFBP1 (FGF binding protein 1) expression in both serum and kidney tissue after AKI suggested a potential contribution to the vascular sensitization. Administration of FGF2 and FGFBP1 proteins to isolated healthy brain vessels mimicked the sensitization to Ang II after AKI. Brain vessels in Fgfbp1-/- AKI mice failed to induce Ang II sensitization. Complementary to this, systemic treatment with the clinically used FGF receptor kinase inhibitor BGJ398 (Infigratinib) reversed the AKI-induced brain vascular sensitization to Ang II. All these findings lead to the conclusion that FGFBP1 is especially necessary for AKI-mediated brain vascular sensitization to Ang II and inhibitors of FGFR pathway may be beneficial in preventing AKI-induced brain vessel injury.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Angiotensin II / Intercellular Signaling Peptides and Proteins / Acute Kidney Injury / Mesenteric Arteries Type of study: Prognostic_studies Limits: Animals Language: En Journal: Hypertension Year: 2020 Document type: Article Affiliation country: Country of publication:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Angiotensin II / Intercellular Signaling Peptides and Proteins / Acute Kidney Injury / Mesenteric Arteries Type of study: Prognostic_studies Limits: Animals Language: En Journal: Hypertension Year: 2020 Document type: Article Affiliation country: Country of publication: